Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy
Abstract With the incorporation of cyclin-dependent kinase inhibitors in early breast cancer (BC), a better identification of biomarkers is needed. The PROMETEO II trial aimed to evaluate the antitumor activity of palbociclib plus letrozole and to identify response biomarkers in patients with operab...
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| Format: | Article |
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Nature Portfolio
2024-11-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-024-00710-x |
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| author | Sonia Pernas Esther Sanfeliu Guillermo Villacampa Javier Salvador Antonia Perelló Xavier González Begoña Jiménez María Merino Patricia Palacios Tomás Pascual Emilio Alba Lorea Villanueva Samyukta Chillara Juan Manuel Ferrero-Cafiero Patricia Galvan Aleix Prat Eva Ciruelos |
| author_facet | Sonia Pernas Esther Sanfeliu Guillermo Villacampa Javier Salvador Antonia Perelló Xavier González Begoña Jiménez María Merino Patricia Palacios Tomás Pascual Emilio Alba Lorea Villanueva Samyukta Chillara Juan Manuel Ferrero-Cafiero Patricia Galvan Aleix Prat Eva Ciruelos |
| author_sort | Sonia Pernas |
| collection | DOAJ |
| description | Abstract With the incorporation of cyclin-dependent kinase inhibitors in early breast cancer (BC), a better identification of biomarkers is needed. The PROMETEO II trial aimed to evaluate the antitumor activity of palbociclib plus letrozole and to identify response biomarkers in patients with operable HR+/HER2- BC and residual disease after neoadjuvant chemotherapy (NAC). The primary endpoint was the rate of complete cell cycle arrest (CCCA), centrally determined by Ki67 ≤ 2.7% at surgery. A comprehensive translational analysis was conducted. At surgery, the CCCA rate was 59.1%, with a 44.2% decrease in Ki67 from the end of NAC. Changes in intrinsic subtypes occurred in 48% of patients, with proliferation genes suppressed, and immune genes more upregulated in tumors with CCCA. Overall, 14% of tumors were classified as PD-L1+ after palbociclib. Nine patients experienced grade 3 adverse events (AEs). Palbociclib showed an anti-proliferative effect, with increased immune infiltration in residual tumors with CCCA. Trial registration: Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy (PROMETEO II) ClinicalTrial.gov number NCT04130152. Study registration; October 17, 2019. |
| format | Article |
| id | doaj-art-78438f11a5ef4e73bef2803507ca9c9e |
| institution | OA Journals |
| issn | 2374-4677 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-78438f11a5ef4e73bef2803507ca9c9e2025-08-20T02:38:33ZengNature Portfolionpj Breast Cancer2374-46772024-11-011011810.1038/s41523-024-00710-xPalbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapySonia Pernas0Esther Sanfeliu1Guillermo Villacampa2Javier Salvador3Antonia Perelló4Xavier González5Begoña Jiménez6María Merino7Patricia Palacios8Tomás Pascual9Emilio Alba10Lorea Villanueva11Samyukta Chillara12Juan Manuel Ferrero-Cafiero13Patricia Galvan14Aleix Prat15Eva Ciruelos16SOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupHospital Universitario Virgen del RocioHospital Son EspasesSOLTI Cancer Research GroupHospitales Regional y Universitario Virgen de la VictoriaHospital Universitario Infanta SofíaHospital Clínico Universitario de SantiagoSOLTI Cancer Research GroupHospital Clínico Universitario Virgen de la Victoria, Málaga. Instituto de Investigación Biomédica de Málaga, IBIMA, Málaga, Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIIISOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupAugust Pi i Sunyer Biomedical Research Institute (IDIBAPS)SOLTI Cancer Research GroupSOLTI Cancer Research GroupAbstract With the incorporation of cyclin-dependent kinase inhibitors in early breast cancer (BC), a better identification of biomarkers is needed. The PROMETEO II trial aimed to evaluate the antitumor activity of palbociclib plus letrozole and to identify response biomarkers in patients with operable HR+/HER2- BC and residual disease after neoadjuvant chemotherapy (NAC). The primary endpoint was the rate of complete cell cycle arrest (CCCA), centrally determined by Ki67 ≤ 2.7% at surgery. A comprehensive translational analysis was conducted. At surgery, the CCCA rate was 59.1%, with a 44.2% decrease in Ki67 from the end of NAC. Changes in intrinsic subtypes occurred in 48% of patients, with proliferation genes suppressed, and immune genes more upregulated in tumors with CCCA. Overall, 14% of tumors were classified as PD-L1+ after palbociclib. Nine patients experienced grade 3 adverse events (AEs). Palbociclib showed an anti-proliferative effect, with increased immune infiltration in residual tumors with CCCA. Trial registration: Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy (PROMETEO II) ClinicalTrial.gov number NCT04130152. Study registration; October 17, 2019.https://doi.org/10.1038/s41523-024-00710-x |
| spellingShingle | Sonia Pernas Esther Sanfeliu Guillermo Villacampa Javier Salvador Antonia Perelló Xavier González Begoña Jiménez María Merino Patricia Palacios Tomás Pascual Emilio Alba Lorea Villanueva Samyukta Chillara Juan Manuel Ferrero-Cafiero Patricia Galvan Aleix Prat Eva Ciruelos Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy npj Breast Cancer |
| title | Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy |
| title_full | Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy |
| title_fullStr | Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy |
| title_full_unstemmed | Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy |
| title_short | Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy |
| title_sort | palbociclib and letrozole for hormone receptor positive her2 negative breast cancer with residual disease after neoadjuvant chemotherapy |
| url | https://doi.org/10.1038/s41523-024-00710-x |
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